Uncontrolled blood pressure despite medical treatmentXx_NEWLINE_xXFor subjects planned to potentially receive bevacizumab, they have no evidence of uncontrolled hypertension (defined as a blood pressure of ? 150 mm Hg systolic and/or ? 100 mm Hg diastolic on medication) or active GI perforationXx_NEWLINE_xXPatients with uncontrolled high blood pressure (i.e., systolic/diastolic blood pressure > 99th percentile) are not eligibleXx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease at the time of study entry, including\r\n* Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg) \r\n* Pulmonary hypertension  \r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air   \r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement  \r\n* Medically significant (symptomatic) bradycardiaXx_NEWLINE_xXPatients must not have inadequately controlled hypertension; patients must have documented blood pressures of systolic blood pressure (SBP) < 150 and diastolic blood pressure (DBP) < 90 within 14 days of starting randomization; blood pressure medications (any number) are permittedXx_NEWLINE_xXPatients with known significant active cardiovascular or pulmonary disease at the time of study entry are INELIGIBLE including:\r\n* Uncontrolled hypertension (i.e., systolic blood pressure >180 mm Hg, diastolic blood pressure > 95 mm Hg); use of anti-hypertensive agents to control hypertension before cycle1 day 1 is allowed\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air\r\n* QT syndrome, or torsades de pointes\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* Medically significant (symptomatic) bradycardia\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital longXx_NEWLINE_xXSystolic blood pressure (BP) =< 150 mg HGXx_NEWLINE_xXBlood pressure that is not controlled despite > 2 oral agents (systolic blood pressure [SBP] > 160 and diastolic blood pressure [DBP] > 90 documented during the screening period with no subsequent blood pressure readings > 160/100)Xx_NEWLINE_xXConcurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatment; if severe hearing impairment is measured or if significant neuropathy is reported at baseline the treating physician will discuss the risks for further permanent hearing loss and neuropathy with the patientXx_NEWLINE_xXPatients with persistently uncontrolled hypertension (systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm Hg) despite optimal medical therapyXx_NEWLINE_xXBlood pressure >140/80Xx_NEWLINE_xXAdequately controlled blood pressureXx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v]4.0) on repeated measurement) despite optimal medical managementXx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease at the time of study registration, including:\r\n* Uncontrolled high blood pressure (i.e., systolic blood pressure > 160 mm Hg, diastolic blood pressure > 95 mm Hg)\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* Medically significant (symptomatic) bradycardia\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXUncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure controlXx_NEWLINE_xXHeart disease including congestive heart failure (New York Heart Association [NYHA] grade II or greater); unstable angina; prior myocardial infarction (non-ST-elevation myocardial infarction [NSTEMI] or ST-elevation myocardial infarction [STEMI]) within 6 months prior to study enrollment; hypertension with a systolic blood pressure of > 150 mm Hg or diastolic blood pressure of >100 mm Hg while on antihypertensive medicationXx_NEWLINE_xXUncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg). Use of antihypertensive agents to control hypertension before week 1, day 1 is allowed.Xx_NEWLINE_xXPatients must demonstrate adequately controlled blood pressure at the time of study entry, as defined by a blood pressure =< 150/100 mmHg at study screening on at least one of two screenings conducted at least 24 hours apart; if blood pressure meets these guidelines on initial measurement, no subsequent measurement for screening is needed; blood pressure may be assessed by automated or manual methods by an appropriately trained clinician or nurseXx_NEWLINE_xXParticipants with uncontrolled high blood pressure, defined as a blood pressure during screening of >= 160/100 despite medical managementXx_NEWLINE_xXHave poorly controlled hypertension defined as blood pressure >160/90 on at least 2 repeated determinations on separate days within 2 weeks (14 days) prior to initiation of screeningXx_NEWLINE_xXClinically significant, uncontrolled heart diseases\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication; initiation or adjustment of antihypertensive medication (s) is allowed prior to screening\r\n* Ventricular arrhythmias\r\n* Supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Fridericia's correction formula (QTcF) > 480 msecXx_NEWLINE_xXNormotensive or well controlled blood pressure (<140/90).Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE v4.0)] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease at the time of study entry, including:\r\n* Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas (ABG) analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* Medically significant (symptomatic) bradycardia\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXPatients with impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* History or presence of serious uncontrolled ventricular arrhythmias\r\n* Any of the following within 6 months prior to starting study drug: myocardial infarction (MI), severe/unstable angina, coronary artery bypass graft (CABG), congestive heart failure (CHF), cerebrovascular accident (CVA), transient ischemic attack (TIA), pulmonary embolism (PE)\r\n* Uncontrolled hypertension (defined as systolic blood pressure [SBP] >= 160 mm Hg or diastolic blood pressure [DBP] >= 100 mm Hg while on anti-hypertensive medications)Xx_NEWLINE_xXNo uncontrolled hypertension (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)Xx_NEWLINE_xXUnstable hypertension (blood pressure > 160/100)Xx_NEWLINE_xXThe patient has uncontrolled hypertension defined as a blood pressure measurement greater than 150 mm Hg systolic or 90 mm Hg diastolic with medicationXx_NEWLINE_xXBlood pressure less than 140/90 mm Hg with or without anti-hypertensive therapy\r\n* Patients may be rescreened after initial ineligibility if due to elevated blood pressure, if adequately medically managed within approximately 30 daysXx_NEWLINE_xXUncontrolled hypertension (systolic pressure >140 mm Hg and/or diastolic pressure > 90 mm Hg [National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease including: a) Uncontrolled hypertension (i.e., systolic blood pressure >180 mm Hg, diastolic blood pressure > 95 mm Hg). Use of anti-hypertensive agents to control hypertension before cycle1 day 1 is allowed. b) Pulmonary hypertension c) Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air d) Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement e) Medically significant (symptomatic) bradycardia f) History of arrhythmia requiring an implantable cardiac defibrillator g) Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes).Xx_NEWLINE_xXHas inadequately controlled hypertension (defined as systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 95 mm Hg); the use of antihypertensive medications to control blood pressure is permitted; retesting is permittedXx_NEWLINE_xXHypertension:\r\n* Patients, 3-17 years of age must have a blood pressure that is =< 95th percentile for age, height and gender at the time of registration\r\n** The normal blood pressure by height, age and gender tables can be accessed in the Generic Forms section of the Pediatric Brain Tumor Consortium (PBTC) members’ webpage\r\n* Patients who are >= 18 years of age must have a blood pressure that is < 140/90 mm of Hg at the time of registration\r\n* Note: if a blood pressure (BP) reading prior to registration is above the 95th percentile for age, height and gender it must be rechecked and documented to be =< the 95th percentile for age, height and gender prior to patient registrationXx_NEWLINE_xXPoorly controlled hypertension (systolic blood pressure [SBP] > 150 or diastolic blood pressure [DBP] > 90 despite antihypertensive therapy)Xx_NEWLINE_xXPatients with clinically significant, uncontrolled cardiovascular disease, such as:\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* Patients with a history of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Peripheral vascular disease\r\n* Patients with uncontrolled hypertension defined as a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medication; initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias\r\n* Supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Patients with corrected QT (QTc) >= 450 ms (male patients) or >= 460 ms (female patients) using Fridericia correction (QTcF) on the screening electrocardiogram (ECG)\r\n* Patients with history of congenital long QT syndrome or history of torsade de pointesXx_NEWLINE_xXAbsence of uncontrolled angina or hypertension defined as sustained blood pressure (BP) > 150 mm Hg systolic or > 100 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatmentXx_NEWLINE_xXUncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical managementXx_NEWLINE_xXMen with baseline systolic blood pressure (SBP) < 110 or heart rate (HR) < 60Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXSustained systolic blood pressure (BP) >140 mm Hg or <90 mm Hg, diastolic BP >100 mm Hg or <60 mm HgXx_NEWLINE_xXPatient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:\r\n* Unstable angina within 6 months prior to screening?\r\n* Myocardial infarction within 6 months prior to screening?\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV);\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication.\r\n* Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening?\r\n* Ventricular arrhythmias\r\n* Supraventricular and nodal arrhythmias not controlled with medication?\r\n* Other cardiac arrhythmia not controlled with medication?\r\n* Corrected QT (QTcF) > 470 ms using Fridericia’s correction on the screening electrocardiography (ECG)Xx_NEWLINE_xXPatients must not have uncontrolled hypertension (systolic >180 mm hg or diastolic > 100 mg Hg), angina pectoris, cardiac dysrhythmia, or recent (within 6 weeks) intracranial hemorrhage.Xx_NEWLINE_xXHypertension defined as sustained BP > 140 millimeter of mercury (mm Hg) systolic, or > 90 mm Hg diastolic within 7 days before the first dose of study treatment and/or receiving medication to treat hypertensionXx_NEWLINE_xXUncontrolled hypertension (that is, either systolic blood pressure > 180 millimeter of mercury [mm Hg] or diastolic blood pressure > 95 mm Hg).Xx_NEWLINE_xXHas uncontrolled hypertension defined as blood pressure > 150/90 on medication(s) by 2 blood pressure readings taken at least 1 hour apart.Xx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease at the time of study entry, including: uncontrolled high blood pressure (i.e., systolic blood pressure > 150 mm Hg, diastolic blood pressure > 90 mm Hg); use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed; pulmonary hypertension; uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air; significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement; medically significant (symptomatic) bradycardia; history of arrhythmia requiring an implantable cardiac defibrillator; baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXTo be performed within 10 business days prior to day 1: In patients who are to receive VRP, base systolic blood pressure (SBP) > 110; diastolic blood pressure (DBP) > 60 and baseline heart rate > 60Xx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease including:\r\n* Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg); use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* Medically significant (symptomatic) bradycardia\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXSystolic blood pressure >140mm Hg or diastolic blood pressure > 90 mm HgXx_NEWLINE_xXUncontrolled hypertension (defined as average systolic blood pressure >= 140 or average diastolic blood pressure >= 90, with blood pressure measured >= 3 times in the two weeks prior to enrollment) or diabetesXx_NEWLINE_xXConcurrent uncontrolled hypertension defined as sustained blood pressure > 95th percentile for age, height and gender (systolic or diastolic) despite optimal antihypertensive treatment within 7 days of the first dose of study treatmentXx_NEWLINE_xXUncontrolled hypertension as defined by systolic blood pressure (SBP) > 150 or diastolic blood pressure (DBP) > 90 on at least two separate occasions documented in the medical record; patients would be eligible if blood pressure is controlled with appropriate anti-hypertensive therapy; rescreening after this therapy has been instituted is allowedXx_NEWLINE_xXSignificant cardiac history:\r\n* History of myocardial infarction or ischemic heart disease within 1 year before first study drug administration;\r\n* Uncontrolled arrhythmia;\r\n*History of congenital QT prolongation;\r\n* New York Heart Association class III or IV cardiac disease;\r\n* Uncontrolled hypertension: blood pressure consistently greater than 150 mm Hg systolic and 100 mm Hg diastolic in spite of antihypertensive medicationXx_NEWLINE_xXClinically significant cardiovascular disease defined as follows: \r\n* Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] > 160 mm Hg and/or diastolic pressure [DBP] > 90 mm Hg despite antihypertensive therapy) \r\n* History of cerebrovascular accident (CVA) within 6 months \r\n* Myocardial infarction or unstable angina within 6 monthsXx_NEWLINE_xXUncontrolled hypertension, systolic blood pressure (SBP) > 160 or diastolic blood pressure (DBP) > 100Xx_NEWLINE_xXPONATINIB \r\n* Patients with cytogenetically ‘favorable risk' AML (core-binding factor leukemias) will not be enrolled on the ponatinib arm; testing with cytogenetics and fluorescence in situ hybridization (FISH) can establish this subtype within 7 days of the diagnostic bone marrow biopsy\r\n* History of acute pancreatitis within 1 year of study or history of chronic pancreatitis\r\n* Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)\r\n* Any history of myocardial infarction, stroke, or revascularization\r\n** Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism with the exception of upper Extremity/Line associated deep vein thrombosis (DVTs) which are adequately treated (line removed and/or patient anti-coagulated)\r\n* Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure controlXx_NEWLINE_xXNo evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 30 minutes apart; the baseline systolic blood pressure readings must be =< 140 mm Hg, and the baseline diastolic blood pressure readings must be =< 90 mm Hg; patients whose hypertension is controlled by antihypertensive therapies are eligibleXx_NEWLINE_xXClinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:\r\n* Unstable angina\r\n* Myocardial infarction\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication\r\n* Ventricular arrhythmias, or supraventricular/nodal arrhythmias not controlled with medications; other cardiac arrhythmias not controlled with medications\r\n* Left ventricular ejection fraction < 20% corrected QT (QTcF) > 470 ms using Fridericia’s correction on the screening electrocardiogram (ECG)\r\n* Initiation or adjustment of antihypertensive medication(s) is allowed prior to screeningXx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease at the time of study entry, including: uncontrolled high blood pressure (i.e., systolic blood pressure >180 mm Hg, diastolic blood pressure > 95 mm Hg); use of anti-hypertensive agents to control hypertension before cycle 1 day 1 is allowed; pulmonary hypertension; uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air; significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement; medically significant (symptomatic) bradycardia; history of arrhythmia requiring an implantable cardiac defibrillator; baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease including:\r\n* Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg); use of anti-hypertensive agents to control hypertension before cycle1 day 1 is allowed\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging\r\nindependent of symptom control with medical intervention, or history of valve\r\nreplacement\r\n* Medically significant (symptomatic) bradycardia\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXSystolic blood pressure =< 160 mg Hg or diastolic pressure =< 90 mg Hg within 14 days prior to study registrationXx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure [SBP] > 170/diastolic blood pressure [DBP] > 105)Xx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease at the time of study entry, including:\r\n* Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* Medically significant (symptomatic) bradycardia\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsade de pointes)Xx_NEWLINE_xXPre-existing uncontrolled hypertension defined as > 150/90 mm Hg with medicationXx_NEWLINE_xXPoorly controlled arterial hypertension (systolic > 150 mm Hg and/or diastolic > 100 mm Hg), with or without antihypertensive medication; patients presenting with high blood pressure are eligible if the dose or adjustment of anti-hypertensive lowers blood pressure to meet the inclusion criteria of the studyXx_NEWLINE_xXPatient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication \r\n** Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Corrected QT (QTcF) > 470 ms using Fridericia’s correction on the screening electrocardiogram (ECG)Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v 4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXHave uncontrolled hypertension (i.e., >150 and >90 for systolic blood pressure (SBP) and diastolic blood pressure (DBP) respectively). Participants with hypertension should be under treatment at study entry to ensure blood pressure control. Those requiring 3 or more antihypertensive medications should be discussed with the medical monitor.Xx_NEWLINE_xXPHASE II COLORECTAL CANCER COHORT 6 (MEDI+C ONLY):\r\nAdequately controlled blood pressure (SBP < 140 mm Hg and DBP < 90mmHg) on a maximum of three anti-hypertensive medicationsXx_NEWLINE_xXSystolic blood pressure (SBP) > 90 (or within 10% of their baseline SBP) and diastolic blood pressure > 50 (or within 10% of their baseline diastolic blood pressure [DBP]) at time of harvestXx_NEWLINE_xXPatients must be willing and able to check and record daily blood pressure readings; blood pressure cuffs will be provided to patients randomized to Arm IIIXx_NEWLINE_xXPatients with high risk of cardiovascular event such as severe uncontrolled hypertension (> 170/110 systemic blood pressure on therapy), or pulmonary hypertension (greater than .5 systolic blood pressure)Xx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure > 140 mm Hg and diastolic blood pressure of > 90 mm Hg which cannot be controlled by anti-hypertensive therapy), congestive heart failure (CHF), or other major medical illnessXx_NEWLINE_xXPatient has clinically significant, uncontrolled heart disease and/or recent cardiac event (within 6 months), such as:\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III-IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication \r\n* Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias\r\n* Supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Corrected QTcF > 470 msec using Fridericia correction on the screening electrocardiogram (ECG)Xx_NEWLINE_xXClinically significant, uncontrolled intercurrent illness including, but not limited to:\r\n* Symptomatic or active infection\r\n* Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control\r\n* Psychiatric illness/social situations that would limit compliance with study requirementsXx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure; [SBP] greater than 180 or diastolic blood pressure; [DBP] greater than 110)Xx_NEWLINE_xXAny of the following concurrent severe and/or uncontrolled medical conditions which could compromise participation in the study; impaired cardiac function or clinically significant cardiac diseases, including any of the following:\r\n* Unstable angina within 6 months prior to screening\r\n* Myocardial infarction within 6 months prior to screening\r\n* History of documented congestive heart failure (New York Heart Association functional classification III - IV)\r\n* Uncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without antihypertensive medication\r\n* Initiation or adjustment of antihypertensive medication(s) is allowed prior to screening\r\n* Ventricular arrhythmias; supraventricular and nodal arrhythmias not controlled with medication\r\n* Other cardiac arrhythmia not controlled with medication\r\n* Corrected QT (QTc) > 450 msec using Fridericia correction on the screening electrocardiogram (ECG)Xx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease at the time of study entry, including:\r\n* Uncontrolled high blood pressure (i.e., systolic blood pressure > 150 mm Hg, diastolic blood pressure > 95 mm Hg)\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* Medically significant (symptomatic) bradycardia\r\n* History of arrhythmia requiring an implantable cardiac defibrillatorXx_NEWLINE_xXUncontrolled hypertension as defined by SBP > 160 mm/Hg or DBP > 100 mm/Hg despite medical therapy.Xx_NEWLINE_xXPatients who are currently receiving a beta-blocker for another medical condition will be excluded from this study; patients with extremes of blood pressure (e.g., systolic blood pressure [SBP] > 150 or < 100) may be excluded from participation if the treating physician feels that this medical condition has not been adequately addressed by the patient’s primary care physicianXx_NEWLINE_xXSystolic blood pressure =< 160 mg Hg or diastolic pressure =< 90 mg Hg within 14 days prior to registrationXx_NEWLINE_xXSystolic blood pressure (BP) > 160 mm Hg or diastolic pressure > 100 mm Hg despite optimal medical managementXx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure [SBP] equal to or more than 140 or diastolic blood pressure [DBP] equal to or more than 90)Xx_NEWLINE_xXPonatinib\r\n* History of acute pancreatitis within 1 year of study or history of chronic pancreatitis\r\n* History of alcohol abuse\r\n* Uncontrolled hypertriglyceridemia (triglycerides > 450 mg/dL)\r\n* Clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:\r\n** Any history of myocardial infarction, stroke, or revascularization\r\n** Unstable angina or transient ischemic attack within 6 months prior to start of study treatment\r\n** Congestive heart failure within 6 months prior to enrollment, or left ventricular ejection fraction (LVEF) less than lower limit of normal per local institutional standards within 6 months prior to enrollment\r\n** History of clinically significant (as determined by the treating physician) atrial arrhythmia\r\n** Any history of ventricular arrhythmia\r\n** Any history of venous thromboembolism including deep venous thrombosis or pulmonary embolism\r\n* Uncontrolled hypertension (diastolic blood pressure > 90 mm Hg; systolic > 140 mm Hg); patients with hypertension should be under treatment on study entry to effect blood pressure control; taking medications that are known to be associated with torsades de pointes\r\n* Taking any medications or herbal supplements that are known to be strong inhibitors of CYP3A4 within at least 14 days before the first dose of ponatinib\r\n* Ocular toxicity present as measured during a comprehensive eye examXx_NEWLINE_xXHypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mm Hg) at screeningXx_NEWLINE_xXAdequately controlled blood pressureXx_NEWLINE_xXUncontrolled high blood pressure (ie, systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)Xx_NEWLINE_xXUncontrolled hypertension defined as an average systolic blood pressure of >= 140 mm Hg or an average diastolic pressure >= 95 mm HgXx_NEWLINE_xXHave diastolic blood pressure of > 90 mm Hg resting at baseline despite medication.Xx_NEWLINE_xXSystolic blood pressure =< 100 mm Hg at baseline, diastolic =< 60 mm Hg at baseline within 4 weeks prior to start of any therapyXx_NEWLINE_xXSymptoms of uncontrolled intracranial pressureXx_NEWLINE_xXTreatment refractory hypertension defined as a blood pressure of systolic > 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapyXx_NEWLINE_xXInadequately controlled hypertension (systolic blood pressure [SBP] > 150mmHg, diastolic blood pressure [DBP] > 100mg Hg)Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXUncontrolled arterial hypertension despite appropriate medical therapy (systolic blood pressure > 160 or diastolic blood pressure > 100)Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure >= 140 mm Hg or diastolic pressure >= 90 mm Hg on repeated measurement) despite optimal medical managementXx_NEWLINE_xXBaseline blood pressure must be adequately controlled with or without antihypertensive medications prior to enrollment (systolic =< 150 mm Hg, diastolic =< 90 mm Hg)Xx_NEWLINE_xXUncontrolled hypertension, defined as systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mm Hg, despite optimal medical managementXx_NEWLINE_xXBlood pressure =< 140/90 within 10 days of registration (must be taken and recorded by a health care professional); Note: if the systolic blood pressure is > 140 and/or diastolic blood pressure is > 90 at the time of registration, the patient’s blood pressure must be controlled; systolic blood pressure must be < 140 and diastolic blood pressure must be < 90 on at least 2 separate measurements prior to the start of treatment, and the treating physician must believe that this is feasible in order to enroll the patientXx_NEWLINE_xXNo clinically significant cardiovascular disease, defined as one of the following:\r\n* Uncontrolled hypertension (blood pressure > 150/100 mm/Hg at the time of enrollment); patients with hypertension and blood pressure =< 150/100 mm Hg on stable antihypertensive regimen are eligible\r\n* History of myocardial infarction or unstable angina < 24 weeks prior to randomization\r\n* New York heart association grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris\r\n* Grade II or greater peripheral vascular diseaseXx_NEWLINE_xXUncontrolled hypertension, defined as systolic > 150 mm Hg or diastolic > 90 mm HgXx_NEWLINE_xXSignificant medical co-morbidities as described below:\r\n* Cardiac disease:\r\n** Congestive heart failure > class II New York Heart Association (NYHA)\r\n** Unstable angina (anginal symptoms at rest), or new-onset angina (begun within the last 3 months), or myocardial infarction within the 6 months prior to enrollment, or\r\n** Cardiac ventricular arrhythmias requiring anti-arrhythmic therapy\r\n** Known history of QTc prolongation or torsades de pointes\r\n* Grade 3 hypertension (systolic blood pressure [SBP] >= 160 mm Hg and/or diastolic blood pressure [DBP] >= 100 mm Hg despite maximal medical therapy)\r\n* Thrombotic, embolic, venous, or arterial events such as a cerebrovascular accident including transient ischemic attacks within the past 6 months\r\n* Known human immunodeficiency virus (HIV) infection or chronic hepatitis B or C\r\n* Previous or concurrent cancer that is distinct in primary site or histology from breast cancer within 5 years prior to enrollment EXCEPT cervical cancer in situ, treated non-melanoma skin cancers, superficial bladder tumors (Ta and Tis)Xx_NEWLINE_xXUncontrolled hypertension (systolic > 150 and/or diastolic > 100 mm Hg)Xx_NEWLINE_xXUncontrolled cardiovascular conditions of hypertension (systolic >180 mm Hg), angina pectoris, or cardiac dysrhythmia; or recent history of intracranial hemorrhageXx_NEWLINE_xXHas poorly controlled hypertension defined as systolic blood pressure (SBP) ?150 mm Hg and/or diastolic blood pressure (DBP) ?90 mm Hg.Xx_NEWLINE_xXUncontrolled hypertension: systolic blood pressure >= 160, diastolic blood pressure >= 90Xx_NEWLINE_xXHave uncontrolled hypertension (systolic blood pressure greater than 150 or diastolic blood pressure greater than 100) or history of congestive heart failure (AHA Grade 2 or higher).Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 (v4.0)] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXUncontrolled blood pressure and hypertension: systolic blood pressure (SBP) > 140 mm Hg or diastolic blood pressure (DBP) > 90 mm Hg within 14 days prior to registration; patients are permitted to be receiving multiple anti-hypertensive medications (unless otherwise indicated in the study); all blood pressure measurements within the 14 days prior to registration and on day 1 of cycle 1 must be SBP =< 140 and DBP =< 90; an exception can be made by a healthcare provider for a patient with a single blood pressure elevation who upon rechecking has a normal blood pressureXx_NEWLINE_xXUncontrolled hypertension (ie, either systolic blood pressure greater than [>] 160 millimeter of mercury [mm Hg]; diastolic blood pressure >95 mm Hg). Use of anti-hypertensive agents to control hypertension before Cycle 1 Day 1 is allowed;Xx_NEWLINE_xXHave an uncontrolled arterial hypertension with systolic blood pressure ?150 or diastolic blood pressure ?90 millimeters of mercury (mm Hg) despite standard medical management.Xx_NEWLINE_xXPatients who are ? 18 years of age must have a systolic blood pressure that is > 160 or diastolic < 90 mm of Hg at the time of enrollmentXx_NEWLINE_xXUncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) v4.03] on repeated measurement) despite optimal medical management.Xx_NEWLINE_xXUncontrolled hypertension, defined as systolic greater than 150 mm Hg or diastolic greater than 90 mm Hg despite antihypertensive medications.Xx_NEWLINE_xXHypertensive patients with uncontrolled blood pressure.Xx_NEWLINE_xXTreatment refractory hypertension systolic blood pressure (SBP) > 140 mm Hg and/or diastolic blood pressure (DBP) > 90 mm HgXx_NEWLINE_xXUncontrolled hypertension (mean systolic blood pressure [BP] >= 160 mm Hg and/or mean diastolic BP >= 100 mm Hg on 3 determinations 5 minutes apart while on 2 anti-hypertensive agents) or hypertension requiring treatment with more than 2 anti-hypertensive agentsXx_NEWLINE_xXPatients with inadequately controlled systemic hypertension (systolic blood pressure [SBP] and/or\r\ndiastolic blood pressure [DBP] > 95th percentile for age and height)\r\n* Patients with a prior history of hypertensive crisis and/or hypertensive encephalopathy\r\nIf a blood pressure (BP) measurement prior to registration is > 95th percentile for age and height, it must be rechecked and documented to be < 95th percentile for age and height prior to registration; if a patient falls between the height or weight percentiles, site should average the value as appropriate; for patients >= 18 years, use adult normal ranges for blood pressure; patients with hypertension are eligible if their blood pressures become < 95th percentile after anti-hypertensive medicationsXx_NEWLINE_xXClinically significant cardiac disease such as history of ventricular arrhythmia requiring therapy, currently uncontrolled hypertension (defined as persistent systolic blood pressure > 150 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications), or any history of symptomatic CHFXx_NEWLINE_xXAdequately controlled blood pressureXx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure [SBP] > 170/ diastolic blood pressure [DBP] > 105)Xx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease at the time of study entry,\r\nincluding:\r\n* Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)\r\n* Pulmonary hypertension\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by ABG (arterial blood gas) analysis or pulse oximetry on room air\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement\r\n* Medically significant (symptomatic) bradycardia\r\n* History of arrhythmia requiring an implantable cardiac defibrillator\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXClinically significant cardiovascular disease including:\r\n* Myocardial infarction within 6 months prior to screening\r\n* Uncontrolled angina within 3 months prior to screening\r\n* Congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subjects with history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multi-gated acquisition (MUGA) scan performed within 3 months results in a left ventricular ejection fraction that is >= 45%\r\n* History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes)\r\n* History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place\r\n* Uncontrolled hypertension as indicated by a resting systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg at screening; patients with initially elevated systolic blood pressure > 170 mm Hg or diastolic blood pressure > 105 mm Hg are eligible if they undergo medical management and are re-screenedXx_NEWLINE_xXUncontrolled hypertension or uncontrolled diabetes within 14 days prior to enrollment\r\n* Sustained systolic blood pressure > 160 or diastolic blood pressure > 100 despite medical therapy; sustained blood sugar > 300 despite medical therapy\r\n* Chronic hypertension or diabetes on appropriate medical therapy does not constitute an exclusion criterionXx_NEWLINE_xXConcurrent uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment within 7 days of the first dose of study treatmentXx_NEWLINE_xXPatients with uncontrolled hypertension (systolic blood pressure [SBP] > 155, diastolic blood pressure [DBP] > 90), unstable coronary disease (unstable angina, evidence of congestive heart failure [CHF], or myocardial infarction [MI] within 6 months of study)Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXWillingness and ability to check and record daily blood pressure readings; blood pressure cuffs will be provided to patientsXx_NEWLINE_xXHas inadequately controlled hypertension (defined as systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 95 mm Hg); the use of antihypertensive medications to control blood pressure is permittedXx_NEWLINE_xXPatients with clinically significant cardiovascular disease; this includes:\r\n* Poorly controlled hypertension (> 140 mm Hg and > 90 mm Hg for systolic and diastolic blood pressure [BP]) are ineligible\r\n* Myocardial infarction or unstable angina within 6 months prior to registration; New York Heart Association (NYHA) grade II or greater congestive heart failure \r\n* Cardiac arrhythmia requiring medicationXx_NEWLINE_xXClinically uncontrolled hypertension (diastolic blood pressure > 90 mm mercury [Hg]; systolic > 140 mm Hg); Note: patients with hypertension should be undergoing treatment at study entry for blood pressure controlXx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg on repeated measurement) despite optimal medical management per physician discretionXx_NEWLINE_xXPoorly controlled hypertension (e.g. systolic >160milimiter (mm) Mercury (Hg) or diastolic >100mm Hg)Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXUncontrolled hypertension (defined as blood pressure > 140/90 mm Hg not controlled with anti-hypertensives)Xx_NEWLINE_xXControlled blood pressure (systolic blood pressure < 140 and diastolic blood pressure < 90) on no more than three anti-hypertensive agents; drug formulations containing two or more anti-hypertensive agents will be counted based on the number of active agents in each formulationXx_NEWLINE_xXSustained systolic blood pressure (BP) >140 mm Hg or <90 mm Hg, diastolic BP >100 mm Hg or <60 mm HgXx_NEWLINE_xXModerate or severe pulmonary hypertension defined as pulmonary arterial systolic pressure (PASP) > 50 mm HgXx_NEWLINE_xXUncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)Xx_NEWLINE_xXPatients must not have uncontrolled hypertension (defined as systolic blood pressure > 140 mm Hg and/or diastolic blood pressure > 90 mm Hg which cannot be controlled by anti-hypertensive therapy)Xx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure [SBP] > 170/diastolic blood pressure [DBP] > 105)Xx_NEWLINE_xXSystolic blood pressure > 100 mm/HgXx_NEWLINE_xXPatients with a history of hypertension must have blood pressure that is adequately controlled on antihypertensives; (< 140/90 mm Hg)Xx_NEWLINE_xXNo evidence of preexisting uncontrolled hypertension; if the patient has a history of or elevated blood pressure at baseline then they must have controlled hypertension documented and confirmed by 2 consecutive blood pressure readings taken within 1 hour; the baseline systolic blood pressure readings must be =< 140 mm Hg, and the baseline diastolic blood pressure readings must be =< 90 mm Hg\r\n* Note: initiation or adjustment of antihypertensive medication(s) is permitted prior to study entry; following antihypertensive medication initiation or adjustment, blood pressure (BP) must be re-assessed three times at approximately 2-minute intervals; at least 24 hours must have elapsed between anti-hypertensive medication initiation or adjustment and BP measurement; these three values should be averaged to obtain the mean diastolic blood pressure and the mean systolic blood pressure; the mean systolic blood pressure (SBP)/diastolic blood pressure (DBP) ratio must be < 140/90 mmHg (OR 150/90 mm Hg, if this criterion is approved by the Huntsman Cancer Institute [HCI] Data Safety Monitoring Committee [DSMC] Chair or Co-chair) in order for a subject to be eligible for the studyXx_NEWLINE_xXBaseline systolic blood pressure (SBP) > 100 mm Hg; this is based on the average of two values-separate seated, resting measurements taken five minutes apart; blood pressure (BP) does not need to be checked in both arms unless a reading is below 110 mm Hg, in which case the other arm can be checked as well; if BP is checked in both arms, the higher value is deemed accurate for calculating the averageXx_NEWLINE_xXFor patients with hypertension at baseline with a systolic pressure greater than 140 or a diastolic pressure greater than 90Xx_NEWLINE_xXBlood pressure < 160/90Xx_NEWLINE_xXPatients must have a systolic blood pressure =< 150 mm Hg and diastolic blood pressure =< 100 mm Hg (the use of antihypertensive medications to achieve these goals is allowed)Xx_NEWLINE_xXBlood pressure that is not controlled despite > 2 oral agents (systolic blood pressure [SBP] > 160 and diastolic blood pressure [DBP] > 90 documented during the screening period with no subsequent blood pressure readings < 160/100)Xx_NEWLINE_xXUncontrolled high blood pressure (systolic blood pressure > 150 mm HgXx_NEWLINE_xXUncontrolled hypertension defined by systolic blood pressure (SBP) > 140 or diastolic blood pressure (DBP) > 90 despite titration of anti-hypertensive medicationsXx_NEWLINE_xXUncontrolled intercurrent illness including, but not limited to:\r\n* Uncontrolled hypertension (for the purpose of this trial, well-controlled hypertension is defined as systolic blood pressure of < 140 mm Hg and diastolic pressure < 90 mm Hg)\r\n** NOTE: the use of anti-hypertensive medication to control hypertension is permitted, provided it is not noted as a prohibited med elsewhere in protocol\r\n* Ongoing or active infection\r\n* Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or \r\n* Psychiatric illness/social situations that would limit compliance with study requirementsXx_NEWLINE_xXNo evidence of preexisting uncontrolled hypertension as documented by 2 baseline blood pressure readings taken at least 1 hour apart; the baseline systolic blood pressure readings must be =< 140, and the baseline diastolic blood pressure readings must be =< 90; patients whose hypertension is controlled by antihypertensive therapies are eligibleXx_NEWLINE_xXPoorly controlled hypertension (e.g. systolic > 180 mm Hg or diastolic > 100 mm Hg)Xx_NEWLINE_xXUncontrolled systemic vascular hypertension (systolic blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg on medication)Xx_NEWLINE_xXUncontrolled hypertension (defined as systolic blood pressure [SBP] and/or diastolic blood pressure [DBP] > 95th percentile for age)Xx_NEWLINE_xXClinically significant cardio-vascular disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension (defined as persistent systolic blood pressure > 160 mm Hg and/or diastolic blood pressure > 100 mm Hg on antihypertensive medications), or any history of symptomatic congestive heart failure (CHF)Xx_NEWLINE_xXb. Uncontrolled hypertension (systolic blood pressure > 150 mm Hg or diastolic blood pressure > 90 mmHg despite optimal medical management)Xx_NEWLINE_xXBlood pressure\r\n* Systolic blood pressure (SBP) < 150 mm/Hg\r\n* Diastolic blood pressure (DBP) < 90 mm/HgXx_NEWLINE_xXPatients must not have uncontrolled hypertension as defined by systolic blood pressure >= 150 mm Hg or diastolic blood pressure >= 90 mm Hg; patient may be eligible once hypertension is adequately controlled with medicationsXx_NEWLINE_xXThe participant has high blood pressure or diabetes that is not well-controlled with medicationXx_NEWLINE_xXHypotension as indicated by systolic blood pressure < 86 millimeters of mercury (mm Hg) at screening;Xx_NEWLINE_xXUncontrolled hypertension defined by a systolic blood pressure (SBP) > 150 and/or a diastolic blood pressure (DBP) > 100 mm Hg with or without anti-hypertensive medicationXx_NEWLINE_xXHistory of newly diagnosed or uncontrolled glaucoma/intraocular pressure > 21 mm Hg as measured by tonographyXx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXUncontrolled hypertension (systolic pressure > 140 mm Hg or diastolic pressure > 90 mm Hg [NCI-CTCAE v4.0] on mean of 3 consecutive readings despite optimal medical management; hypertension may be corrected by adding or adjusting antihypertensives prior to the initiation of treatment at the discretion of the practitionerXx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure > 150 or diastolic blood pressure > 100)Xx_NEWLINE_xXParticipants with uncontrolled sustained hypertension which will be defined as systolic blood pressure > 140, and diastolic blood pressure > 90, even with use of anti-hypertensive medicationsXx_NEWLINE_xXHas NYHA Class III or IV heart failure or uncontrolled hypertension (SBP ?160 mm Hg; DBP ?100 mm Hg).Xx_NEWLINE_xXUncontrolled hypertension defined by a systolic blood pressure (SBP) >= 160 mm Hg and/or diastolic blood pressure (DBP) >= 100 mm Hg, with or without anti-hypertensive medicationXx_NEWLINE_xXThe subject has uncontrolled hypertension defined as sustained blood pressure (BP) > 140 mm Hg systolic, or > 90 mm Hg diastolic despite optimal antihypertensive treatment (BP must be controlled at screening)Xx_NEWLINE_xXHypertension which is not controlled to systolic < 160 mm Hg and diastolic < 90 mm Hg;Xx_NEWLINE_xXUncontrolled cardiopulmonary dysfunction (e.g., high blood pressure, serious cardiac\n             arrhythmia)Xx_NEWLINE_xXRecent (< 6 months) myocardial infarction, unstable angina, coronary artery bypass surgery (CABG) or stent placement in the last 2 years, difficult-to-control congestive heart failure, uncontrolled hypertension (systolic blood pressure > 160 mm or a diastolic blood pressure [BP] > 110 mm under normal conditions and while on appropriate anti-hypertensive medications), or difficult-to-control cardiac arrhythmiasXx_NEWLINE_xXClinically significant cardiac disease (class III, or IV of the New York Heart Association classification; unstable angina pectoris, myocardial infarction within 6 months or is post angioplasty or stenting within 6 months; clinically significant cardiac arrhythmia, or uncontrolled hypertension (i.e., systolic blood pressure > 150 mm Hg, diastolic blood pressure > 90 mmHg) despite anti-hypertensive medication;Xx_NEWLINE_xXHypertension: systolic blood pressure (SBP) > 150 or diastolic blood pressure (DBP) > 100 mm mercury (Hg) despite antihypertensive medicationsXx_NEWLINE_xXParticipants must have a baseline blood pressure of 160/90 or less; participants requiring medicines to control blood pressure are eligibleXx_NEWLINE_xXUncontrolled hypertension, defined as systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg, despite medical managementXx_NEWLINE_xXUncontrolled arterial hypertension despite appropriate medical therapy (defined as systolic blood pressure > 160 or diastolic blood pressure > 100)Xx_NEWLINE_xXUncontrolled glaucoma with intraocular pressure greater than (>) 21 millimeters of mercury (mm Hg)Xx_NEWLINE_xXTreatment refractory hypertension defined as a blood pressure of systolic >140 mmHg and/or diastolic >90 mm Hg which cannot be controlled by anti-hypertensive therapyXx_NEWLINE_xXAbnormal systolic blood pressure, diastolic blood pressure and/or heart rateXx_NEWLINE_xXPatients with New York Heart Association (NYHA) grade 2 or higher congestive heart failure, myocardial infarction within the last 6 months, unstable angina pectoris, or arterial thrombotic event with the past 12 months, uncontrolled hypertension (systolic blood pressure > 150 and/or diastolic blood pressure > 100 on antihypertensive medications; patients not on medication for high blood pressure who are found to have systolic blood pressure [SBP] > 150 and/or diastolic blood pressure [DBP] > 100 should have 3 documented episodes of elevated blood pressure before being considered ‘uncontrolled’, if they have 3 documented episodes of elevated blood pressure, then can be started on antihypertensive medications; patients currently on antihypertensive medications with elevated blood pressures as defined above may have their medications adjusted; if patients have persistent [3 episodes] of high blood pressure despite medication adjustment they will be considered ineligible for study participation; each measured episode should be 24 hours apart), prior history of hypertensive crisis or hypertensive encephalopathy, uncontrolled or clinically significant arrhythmia, grade II or greater peripheral vascular disease or prior history of stroke or transient ischemic attack (TIA); patient must have a pretreatment oncocardiology echocardiogram with left ventricular ejection fraction (LVEF) above lower limit of normalXx_NEWLINE_xXThe patient has uncontrolled hypertension despite adequate therapy (ie, systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 90 mm Hg found on 2 separate occasions separated by 1 week).Xx_NEWLINE_xXControlled blood pressure, defined as blood pressure =< 140/90 on average (3 separate readings taken at screening visit in a relaxed clinical environment and averaged)Xx_NEWLINE_xXBlood pressure > 140/90 mm/Hg on average (3 separate readings taken at screening visit in a relaxed clinical environment and averaged)Xx_NEWLINE_xXSupine systolic blood pressure < 90 mm Hg, or symptomatic orthostatic hypotension, or a decrease in systolic blood pressure upon standing of > 20 mm Hg despite medical management (e.g. midodrine, fludrocortisones)Xx_NEWLINE_xXNo history of uncontrolled hypertension (blood pressure > 160/100 mm Hg despite anti-hypertensive medication)Xx_NEWLINE_xXClinically significant cardiovascular disease defined as follows:\r\n* Inadequately controlled hypertension (i.e., systolic blood pressure [SBP] > 160 mm Hg and/or diastolic blood pressure [DBP] > 90 mm Hg despite antihypertensive therapy)\r\n* History of cerebrovascular accident (CVA) within 6 months\r\n* Myocardial infarction or unstable angina within 6 months\r\n* New York Heart Association classification II, III, or IV cardiovascular disease\r\n* Serious and inadequately controlled cardiac arrhythmia\r\n* Significant vascular disease (i.e., aortic aneurysm, history of aortic dissection)\r\n* Clinically significant peripheral vascular diseaseXx_NEWLINE_xXHave uncontrolled hypertension (systolic blood pressure greater than 150mmHg or diastolic blood pressure greater than 100mmHg); or history of congestive heart failure (equal to or greater than Grade 2).Xx_NEWLINE_xXAdequate Blood Pressure Control defined as: Blood pressure <= the 95th percentile for age, height, and gender.Xx_NEWLINE_xXCardiovascular disorders including\r\n* Congestive heart failure (CHF): New York Heart Association (NYHA) class III (moderate) or class IV (severe) at the time of screening\r\n* Concurrent uncontrolled hypertension defined as sustained blood pressure (BP) >= 150 mm Hg systolic, or >= 90 mm Hg diastolic despite optimal antihypertensive treatment (Note: if there is any BP measurement that is performed within the screening period that is < 150 mm Hg systolic and < 90 mm Hg diastolic, then BP does not meet definition of sustained)\r\n* Any congenital history of long QT syndrome\r\n* Any of the following within 6 months before the first dose of study treatment:\r\n** Unstable angina pectoris\r\n** Clinically-significant cardiac arrhythmias\r\n** Stroke (including transient ischemic attack [TIA], or other ischemic event)\r\n** Myocardial infarction\r\n** Thromboembolic event requiring therapeutic anticoagulation (Note: subjects with a venous filter [e.g. vena cava filter] are not eligible for this study)Xx_NEWLINE_xXAdequate blood pressure defined as:\r\n* A blood pressure (BP) =< the 95th percentile for age, height, and gender measured; adequate blood pressure can be achieved using medication for treatment of hypertensionXx_NEWLINE_xXPatients not achieving adequate blood pressure in spite of antihypertensive therapy for control of blood pressureXx_NEWLINE_xXPatients must have normal blood pressure or well-controlled hypertension.Xx_NEWLINE_xXUncontrolled hypertension defined as optimally treated baseline blood pressure that exceeds 140/90 mm Hg despite optimal medical managementXx_NEWLINE_xXPatients with clinically significant cardiovascular or cerebrovascular disease:\r\n* History of cerebrovascular accident or transient ischemic attack within past 6 months\r\n* Uncontrolled hypertension, defined as blood pressure > 150/100 mm Hg or systolic blood pressure (BP) > 180 mm Hg if diastolic blood pressure < 90 mm Hg, on at least 2 repeated determinations on separate days within past 3 months\r\n* Myocardial infarction, coronary artery bypass graft (CABG) or unstable angina within the past 6 Months\r\n* New York Heart Association grade III or greater congestive heart failure, serious cardiac arrhythmia requiring medication, unstable angina pectoris within past 6 months\r\n* Clinically significant peripheral vascular disease within past 6 months\r\n* Pulmonary embolism, deep vein thrombosis (DVT), or other thromboembolic event within past 6 monthsXx_NEWLINE_xXHypertension not controlled by medical therapy (systolic blood pressure greater than 150 mm Hg or diastolic blood pressure greater than 100 mm Hg)Xx_NEWLINE_xXUncontrolled hypertension, defined as systolic > 140 mm Hg or diastolic > 90 mm HgXx_NEWLINE_xXIntraocular pressure greater than 21mm Hg as measured by tonography.Xx_NEWLINE_xXTreatment refractory hypertension defined as a blood pressure of systolic> 140 mmHg and/or diastolic > 90 mm Hg which cannot be controlled by anti-hypertensive therapyXx_NEWLINE_xXPreexisting cardiovascular disease. The only exception being well controlled essential hypertension with a sitting blood pressure (B.P.) of < 160 systolic and < 90 diastolic without any evidence of structural heart disease or one episode of myocardial infarction > 8 months ago. A past history of any of the following conditions is considered as exclusions to study participation:Xx_NEWLINE_xXPoorly controlled high blood pressureXx_NEWLINE_xXSignificant active cardiovascular or pulmonary disease including:\r\n* Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg); use of anti-hypertensive agents to control hypertension before cycle1 day 1 is allowed,\r\n* Pulmonary hypertension,\r\n* Uncontrolled asthma or oxygen (O2) saturation < 90% by arterial blood gas analysis or pulse oximetry on room air,\r\n* Significant valvular disease; severe regurgitation or stenosis by imaging independent of symptom control with medical intervention, or history of valve replacement,\r\n* Medically significant (symptomatic) bradycardia,\r\n* History of arrhythmia requiring an implantable cardiac defibrillator,\r\n* Baseline prolongation of the rate-corrected QT interval (QTc) (e.g., repeated demonstration of QTc interval > 480 milliseconds, or history of congenital long QT syndrome, or torsades de pointes)Xx_NEWLINE_xXClinically significant hypotension (systolic blood pressure [SBP] < 80 mm HG or symptomatic)Xx_NEWLINE_xXSystolic blood pressure =< 160 mg Hg or diastolic pressure =< 90 mg Hg within 14 days prior to registrationXx_NEWLINE_xXPatients must have a systolic blood pressure >= 80 mm Hg within 14 days prior to registrationXx_NEWLINE_xXPatients with systolic blood pressure < 90 mm HgXx_NEWLINE_xXBlood pressure <=Grade 1 (hypertensive participants are permitted if their blood pressure is controlled to <=Grade 1 by hypertensive medications.Xx_NEWLINE_xXBlood pressure ?Grade 1 (hypertensive participants are permitted if their blood pressure is controlled to ? Grade 1 by hypertensive medications and glycosylated hemoglobin is ?6.5%).Xx_NEWLINE_xXUncontrolled hypertension (defined by a SBP ? 160 mm Hg or DBP ? 100 mm Hg while on anti-hypertensive medications) within 14 days prior to registration.Xx_NEWLINE_xXPresence of conditions where significant elevations in blood pressure would be a serious hazardXx_NEWLINE_xXStage 2 hypertension or greater (systolic blood pressure > 160 and/or diastolic blood pressure > 100)Xx_NEWLINE_xXResting blood pressure and/or heart rate within normal limitsXx_NEWLINE_xXResting blood pressure and/or heart rate outside normal limitsXx_NEWLINE_xXSignificant cardiovascular disease precluding an exercise program, including recent (within 6 months) myocardial infarction or stroke, pulmonary edema, myocarditis, pericarditis, unstable angina, pulmonary embolism/deep venous thrombosis (PE/DVT), uncontrolled hypertension (systolic blood pressure [SBP] > 200; diastolic blood pressure [DBP] > 110), uncontrolled arrhythmia, heart failure; orXx_NEWLINE_xXResting blood pressure > 160/100Xx_NEWLINE_xXUncontrolled hypertension >= 2 times as noted in medical history (diastolic blood pressure > 100, systolic > 160) =< 90 days prior to registrationXx_NEWLINE_xXLow resting systolic blood pressure: < 90 mm hemoglobin (Hg)Xx_NEWLINE_xXUse of any other blood pressure lowering medication for treatment of hypertension, within 30 days of randomizationXx_NEWLINE_xXResting systolic blood pressure (SBP) > 180 mm HG and/or diastolic blood pressure (DBP) > 100 mm HG, or resting heart rate > 100 beats per minute at the baseline assessmentXx_NEWLINE_xXUncontrolled hypertension (systolic pressure >140 mm Hg or diastolic pressure > 90 mm Hg [National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v)4.0] on repeated measurement) despite optimal medical managementXx_NEWLINE_xXPressure readings >= 140/90 mm Hg, as defined by the 7th Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, will be deemed ineligible to participate and excluded from the study; they will be referred to their family physician or community services; those ineligible based on their initial blood pressure reading are allowed to participate if they provide a letter from a physician who will continue to monitor the participant during the research studyXx_NEWLINE_xXExhibits symptomatic or persistent, uncontrolled hypertension (BP > or = to 140 and/or diastolic pressure of > or = to 90 mm Hg).Xx_NEWLINE_xXSitting systolic BP > 90 mm HgXx_NEWLINE_xXUncontrolled hypertension (defined as blood pressure in adults > 150/95)\r\n* Patients on anti-hypertensive medications are eligible if blood pressure is controlledXx_NEWLINE_xXNo history of hypotension (defined as resting systolic blood pressure of < 110 mm Hg or diastolic blood pressure of < 70 mm Hg) or orthostasis (defined as drop in systolic blood pressure of > 20 mm Hg or increase in HR of > 20 from supine to standing position)Xx_NEWLINE_xXPatients with resting hypotension (blood pressure [BP] < 90/50 mm Hg), or resting hypertension (BP > 170/110 mm Hg) at screeningXx_NEWLINE_xXWithin the past month:\r\n* Heart attack\r\n* Unstable or stable angina (cardiac chest pain)\r\n* Left main coronary artery disease\r\n* Symptomatic heart failure\r\n* Uncontrolled hypertension (systolic blood pressure [SBP] > 180 mm Hg or diastolic blood pressure [DBP] > 100mm Hg)\r\n* Severe valvular heart disease\r\n* Uncontrolled metabolic disease (diabetes with fasting blood sugar [BS] > 300 mg/dl, thyrotoxicosis, myxedema)\r\n* Aortic aneurism (> 45 mm diameter) or aortic dissection\r\n* Hypertrophic obstructive cardiomyopathyXx_NEWLINE_xXUncontrolled severe hypertension at enrollment. Severe hypertension is defined as a systolic or diastolic blood pressure (BP) > 5 mm Hg above the 95th percentile as defined by the National High Blood Pressure Education Program Working Group (NHBPEP) established guidelines for the definition of normal and elevated blood pressure in childrenXx_NEWLINE_xXUncontrolled hypertension (blood pressure > 160/95 mm Hg)Xx_NEWLINE_xXHigh blood pressureXx_NEWLINE_xXHigh blood pressureXx_NEWLINE_xXParticipants with a blood pressure >= 140/90 at the time of baseline testingXx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure [SBP] greater than 180 or diastolic blood pressure [DBP] greater than 110)Xx_NEWLINE_xXParticipants must not have blood pressure < 95 mm Hg systolicXx_NEWLINE_xXUncontrolled hypertension (systolic blood pressure; SBP greater than 180 or diastolic blood pressure; DBP greater than 110)Xx_NEWLINE_xXNormotensive or controlled blood pressure (< 140/90) on a single anti-hypertensive medicationXx_NEWLINE_xXBlood pressure > 140/90 at baseline by home monitoringXx_NEWLINE_xXPatients with hypertension not adequately controlled by medication (i.e. systolic blood pressure >= 150 and/or diastolic blood pressure >= 90 on at least two separate readings)Xx_NEWLINE_xXHave at least one other component of metabolic syndrome reported below:\r\n* Elevated triglycerides (>= 150 mg/dL [1.7 mmol/L]) or on drug treatment for elevated triglycerides \r\n* Reduced high-density lipoprotein-cholesterol (HDL-C) (< 50 mg/dL [1.3 mmol/L]) or on drug treatment for reduced HDL-C\r\n* Elevated blood pressure (>= 130 mm mercury [Hg] systolic blood pressure or >= 85 mm Hg diastolic blood pressure) or on antihypertensive drug treatment in a patient with a history of hypertension\r\n* Elevated fasting glucose (>= 100 mg/dL)Xx_NEWLINE_xXHypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm mercury [Hg] or diastolic blood pressure greater than 100 mm Hg)Xx_NEWLINE_xXhigh blood pressure (defined as systolic blood pressure over 165 or diastolic blood pressure over 100),Xx_NEWLINE_xXPoorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg; the addition of anti-hypertensives to control blood pressure is allowedXx_NEWLINE_xXPoorly controlled hypertension, defined as systolic blood pressure at study entry greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg; the addition of anti-hypertensives to control blood pressure is allowedXx_NEWLINE_xXActive cardiac disease including any of the following:\r\n* Severe congestive heart failure (class IV in accordance with the classification of the New York Heart Association)\r\n* Unstable angina\r\n* Severe arrhythmia (i.e. ventricular tachycardia, flutter fibrillation; ventricular premature complexes occurring close to the preceding T- wave, multifocal complexes)\r\n* Myocardial infarction within 14 days prior to the date of proposed Definity administration\r\n* Uncontrolled systemic hypertension (systolic blood pressure [BP] > 180 mm Hg and/or diastolic BP > 100 mm Hg) despite optimal medical managementXx_NEWLINE_xXPoorly controlled hypertension, with blood pressure at study entry > 160/100; the addition of anti-hypertensives to control blood pressure is allowed for eligibility determinationXx_NEWLINE_xXPoorly controlled hypertension, with blood pressure at study entry > 160/100Xx_NEWLINE_xXSystolic blood pressure < 90 prior to propranololXx_NEWLINE_xXSystolic blood pressure greater than 145 and diastolic blood pressure greater than 90Xx_NEWLINE_xXUncontrolled hypertension defined as persistent systolic blood pressure > 180 mm Hg, or diastolic blood pressure > 110 mm Hg; subjects with known HTN should be stable within these ranges while under pharmaceutical therapy.Xx_NEWLINE_xXSubjects with uncontrolled hypertension defined as persistent systolic blood pressure > 150 mm Hg, or diastolic blood pressure > 95 mm Hg; those subjects with known HTN should be stable within these ranges while under pharmaceutical therapyXx_NEWLINE_xXThe participant has uncontrolled hypertension defined as systolic blood pressure greater than or equal to 180 millimeters of mercury (mm Hg) or diastolic blood pressure greater than or equal to 130 mm Hg.Xx_NEWLINE_xXThe participant has uncontrolled hypertension defined as systolic blood pressure greater than or equal to 180 millimeters of mercury (mm Hg) or diastolic blood pressure greater than or equal to 130 mm Hg.Xx_NEWLINE_xXSubjects with uncontrolled hypertension defined as persistent systolic blood pressure > 180 mm Hg, or diastolic blood pressure > 110 mm Hg; those subjects with known HTN should be under these values while under pharmaceutical therapyXx_NEWLINE_xXBlood pressure <= Grade 1 (hypertensive participants are permitted if their blood pressure is controlled to <= Grade 1 by hypotensive medications and glycosylated HbA1C <= 6.5%).Xx_NEWLINE_xX